Response kinetics of IgG antibodies against SARS-CoV-2 targets: comparing vaccinated and non-vaccinated US clinical patients through linear analysis of Binding Antibody Units Restricted; Files Only

Sandford, Ryan (Spring 2023)

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This study discusses the importance of measuring antibody levels in the blood to understand SARS-CoV- 

2 infections and immune responses. Differences in disease severity and vulnerability based on age, health 

condition, and sex have been identified since the pandemic began in early 2020. However, detecting 

present and past infections using serological data is still evolving, and the saturation of COVID-19

literature can introduce misclassification and selection bias. Standardization of lab protocols and assays 

using WHO ratios and measurements is being pursued, but changes in variant prevalence and repeated 

waves of infections can complicate scientific determinations. This study was sourced from the Flu VE Network 

and CDC Cares Act funding and used cross-sectional data from seven sentinel sites in the US. A 7plex assay was 

used to analyze IgG antibodies of both Receptor Binding Domain (RBD) and Nucleocapsid Proteins (NP) for linear 

analysis of COVID-19 antibody response by health condition, vaccination status, age, sex, and race, as well as RBD

and NP levels at baseline as predictors of antibody change over time. The study examined the relationship 

between COVID-19 vaccine doses, RBD levels, and COVID-19 positivity through analysis of acute samples (2,576) 

and paired analysis (218). This thesis filled several important gaps in the literature on COVID-19 antibody 

responses as measured by RBD and NP BAU levels. The study found that having a breakthrough infection, as 

indicated by a positive COVID-19 PCR test at the acute visit, was associated with a significantly lower level of anti- 

RBD antibody. This result was significant after controlling for key demographic factors as well as the time between 

the last vaccine and the acute visit, and the number of vaccine doses. Hence, this implies that vaccinated 

individuals with a more robust or persistent anti-RBD response are relatively protected from breakthrough 

infection compared to those individuals with a less robust response. Since this analysis controlled for the number 

of vaccine doses, we cannot determine from this analysis the contribution of differences in vaccine number to this 

effect, which could be further explored in analysis stratified by vaccine number.

Table of Contents

1) Background

2) Last Immune Event and COVID Waves

3) Aim 1: Examine the relationship between vaccination and IgG response.

4) Aim 2: Focusing on breakthrough infections (i.e., vaccinated subset only), examine the relationship between pre-existing medical conditions, demographic variables, and specific 5) vaccination characteristics on acute and convalescent IgG responses.

5) Manuscript


7) Immunological Response

8) Targets

9)Site Specific Cross Sectional Sampling

10) Descriptive Statistics for Overall-Sample-Set

11) Aim 1a: Vaccination and Antibody Titers

12) Sensitivity Analysis:

13) Aim1b: Vaccine Only Comparison

14) Descriptive Statistics for Paired Sub-Set

15) Aim2a: Health Condition and Immune Response

16) Analysis 2: NP at Baseline Predicting NP Change (logistic regression)

17) Aim2b: Health Conditions

18) Follow Up at +10 Days

About this Master's Thesis

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  • English
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